This is a 371 of international application PCT/EP99/03153 with international filing date of May 7, 1991 published in English.
The invention relates to compounds with a 3-substituted 5-aryl-4-isoxazolecarbonitrile structure, of formula (I) 
wherein
R is hydrogen, halogen, COOH, COORxe2x80x3, C1-C4 alkyl, NO2, ORxe2x80x3, phenyl;
Rxe2x80x2 is C1-C4 alkyl, COOH, COORxe2x80x3;
Rxe2x80x3 is C1-C4 alkyl;
X is an oxygen or sulfur atom or a single bond;
n is an integer 1-6,
with the proviso that, when Rxe2x80x2 is CH3, R is different from hydrogen;
said compounds having antiviral activity.
In Acts of the First Italian-Swiss Meeting of Medicinal Chemistry (Turin, 1997) derivatives of formula (I) with R=H and Rxe2x80x2=CH3 supposedly having antiviral activity, are cited. It has now been found that both said derivatives and those of formula (I) with R different from hydrogen, have indeed antiviral activity which is of great interest as far as a series of viruses, are concerned.
The invention also relates to pharmaceutical compositions containing as active ingredient at least one compound of formula (I) wherein Rxe2x80x2, Rxe2x80x3, X and n have the meanings defined above, whereas R is hydrogen, also when Rxe2x80x2=CH3, optionally combined with one or more other active principles.
Preferred compounds of formula (I) in the compositions according to the invention are those wherein R is hydrogen, bromine, COOH, COOCH3, CH3, NO2; Rxe2x80x2 is CH3; X is an oxygen atom; n is 2, 3 or 4. Particularly preferred are those compounds wherein R is at the 4-position on the phenyl ring.
According to the invention, compounds (I) are obtained by reacting an intermediate of formula (II) with a 5-(4-hydroxyphenyl)-4-isoxazolecarbonitrile having a Rxe2x80x2S substituent at the 3-position, for example with 3-methylthio-5-(4-hydroxyphenyl)-4-isoxazolecarbonitrile (III), according to scheme A shown hereinbelow: 
wherein R, X and n have the meanings defined above, whereas Z is a halogen atom, preferably a bromine atom.
Intermediate (III) is obtained following scheme B; intermediates of formula (III) wherein the methyl group is substituted by carboxyl or carbalkoxyl can be prepared analogously, 
whereas intermediates (II) can be prepared according to per se known methods.
The reaction yielding final compounds (I), according to scheme A, is suitably carried out in the presence of an acid-binding agent, for example potassium carbonate, in inert solvents, at temperatures ranging from room temperature to about 100xc2x0 C. Suitable solvents are, for example, ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone, or ethers such as tetrahydrofuran or dioxane.